Peptide NMHRYPNQ of the Cellular Prion Protein (PrPC) Inhibits Aggregation and Is a Potential Key for Understanding Prion-Prion Interactions

Dirk Rehders; Birgit Claasen; Lars Redecke; Alexander Buschke; Caroline Reibe; Nico Jehmlich; Martin von Bergen; Christian Betzel; Bernd Meyer

doi:10.1016/j.jmb.2009.07.014

Peptide NMHRYPNQ of the Cellular Prion Protein (PrP^C) Inhibits Aggregation and Is a Potential Key for Understanding Prion-Prion Interactions

Dirk Rehders, Birgit Claasen, Lars Redecke, Alexander Buschke, Caroline Reibe, Nico Jehmlich, Martin von Bergen, Christian Betzel, Bernd Meyer

Institute of Biochemistry

University of Hamburg

6 Citations (Scopus)

Abstract

Pathogenesis of transmissible spongiform encephalopathies is correlated with a conversion of the normal cellular form of the prion protein (PrP^C) into the abnormal isoform (scrapie form of PrP). Contact of the normal PrP with its abnormal isoform, the scrapie form of PrP, induces the transformation. Knowledge of molecules that inhibit such contacts leads to an understanding of the mechanism of the aggregation, and these molecules may serve as leads for drugs against transmissible spongiform encephalopathies. Therefore, we screened a synthetic octapeptide library of the globular domain of the human PrP^C for binding affinity to PrP^C. Two fragments with binding affinity, 149YYRENMHR156 and 153NMHRYPNQ160, were identified with K_d values of 21 and 25 μM, respectively. A 10-fold excess of peptide 153NMHRYPNQ160 inhibits aggregation of the PrP by 99%. NMR and mass spectrometry showed that the binding region of the peptide 153NMHRYPNQ160 is located at helix 3 of the PrP.

Original language	English
Journal	Journal of Molecular Biology
Volume	392
Issue number	1
Pages (from-to)	198-207
Number of pages	10
ISSN	0022-2836
DOIs	https://doi.org/10.1016/j.jmb.2009.07.014
Publication status	Published - 11.09.2009

Funding

This work was supported by Deutsch Forschungsgemeinschaft through SFB470/B2, Graduate College GRK464 and an equipment grant for the 700-MHz NMR spectrometer.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)

Access to Document

10.1016/j.jmb.2009.07.014

Cite this

@article{5ac0946813844a92a5d9127fb76debc6,

title = "Peptide NMHRYPNQ of the Cellular Prion Protein (PrPC) Inhibits Aggregation and Is a Potential Key for Understanding Prion-Prion Interactions",

abstract = "Pathogenesis of transmissible spongiform encephalopathies is correlated with a conversion of the normal cellular form of the prion protein (PrPC) into the abnormal isoform (scrapie form of PrP). Contact of the normal PrP with its abnormal isoform, the scrapie form of PrP, induces the transformation. Knowledge of molecules that inhibit such contacts leads to an understanding of the mechanism of the aggregation, and these molecules may serve as leads for drugs against transmissible spongiform encephalopathies. Therefore, we screened a synthetic octapeptide library of the globular domain of the human PrPC for binding affinity to PrPC. Two fragments with binding affinity, 149YYRENMHR156 and 153NMHRYPNQ160, were identified with Kd values of 21 and 25 μM, respectively. A 10-fold excess of peptide 153NMHRYPNQ160 inhibits aggregation of the PrP by 99\%. NMR and mass spectrometry showed that the binding region of the peptide 153NMHRYPNQ160 is located at helix 3 of the PrP.",

author = "Dirk Rehders and Birgit Claasen and Lars Redecke and Alexander Buschke and Caroline Reibe and Nico Jehmlich and \{von Bergen\}, Martin and Christian Betzel and Bernd Meyer",

note = "Funding Information: This work was supported by Deutsch Forschungsgemeinschaft through SFB470/B2, Graduate College GRK464 and an equipment grant for the 700-MHz NMR spectrometer. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2009",

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doi = "10.1016/j.jmb.2009.07.014",

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T1 - Peptide NMHRYPNQ of the Cellular Prion Protein (PrPC) Inhibits Aggregation and Is a Potential Key for Understanding Prion-Prion Interactions

AU - Rehders, Dirk

AU - Claasen, Birgit

AU - Redecke, Lars

AU - Buschke, Alexander

AU - Reibe, Caroline

AU - Jehmlich, Nico

AU - von Bergen, Martin

AU - Betzel, Christian

AU - Meyer, Bernd

N1 - Funding Information: This work was supported by Deutsch Forschungsgemeinschaft through SFB470/B2, Graduate College GRK464 and an equipment grant for the 700-MHz NMR spectrometer. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2009/9/11

Y1 - 2009/9/11

N2 - Pathogenesis of transmissible spongiform encephalopathies is correlated with a conversion of the normal cellular form of the prion protein (PrPC) into the abnormal isoform (scrapie form of PrP). Contact of the normal PrP with its abnormal isoform, the scrapie form of PrP, induces the transformation. Knowledge of molecules that inhibit such contacts leads to an understanding of the mechanism of the aggregation, and these molecules may serve as leads for drugs against transmissible spongiform encephalopathies. Therefore, we screened a synthetic octapeptide library of the globular domain of the human PrPC for binding affinity to PrPC. Two fragments with binding affinity, 149YYRENMHR156 and 153NMHRYPNQ160, were identified with Kd values of 21 and 25 μM, respectively. A 10-fold excess of peptide 153NMHRYPNQ160 inhibits aggregation of the PrP by 99%. NMR and mass spectrometry showed that the binding region of the peptide 153NMHRYPNQ160 is located at helix 3 of the PrP.

AB - Pathogenesis of transmissible spongiform encephalopathies is correlated with a conversion of the normal cellular form of the prion protein (PrPC) into the abnormal isoform (scrapie form of PrP). Contact of the normal PrP with its abnormal isoform, the scrapie form of PrP, induces the transformation. Knowledge of molecules that inhibit such contacts leads to an understanding of the mechanism of the aggregation, and these molecules may serve as leads for drugs against transmissible spongiform encephalopathies. Therefore, we screened a synthetic octapeptide library of the globular domain of the human PrPC for binding affinity to PrPC. Two fragments with binding affinity, 149YYRENMHR156 and 153NMHRYPNQ160, were identified with Kd values of 21 and 25 μM, respectively. A 10-fold excess of peptide 153NMHRYPNQ160 inhibits aggregation of the PrP by 99%. NMR and mass spectrometry showed that the binding region of the peptide 153NMHRYPNQ160 is located at helix 3 of the PrP.

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